rs7077757

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001134363.3(RBM20):c.1527+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,444,144 control chromosomes in the GnomAD database, including 32,985 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3489 hom., cov: 32)

Exomes 𝑓: 0.21 ( 29496 hom. )

Consequence

RBM20
NM_001134363.3 splice_region, intron

Scores

Splicing: ADA: 0.00001230

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.123

Publications

15 publications found

Variant links:

Genes affected

RBM20 (HGNC:27424): (RNA binding motif protein 20) This gene encodes a protein that binds RNA and regulates splicing. Mutations in this gene have been associated with familial dilated cardiomyopathy. [provided by RefSeq, Apr 2014]

RBM20 Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
dilated cardiomyopathy 1DD
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hypertrophic cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

RBM20 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 10-110784897-C-T is Benign according to our data. Variant chr10-110784897-C-T is described in ClinVar as Benign. ClinVar VariationId is 43975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3 link	c.1527+8C>T	splice_region_variant, intron_variant	Intron 5 of 13	ENST00000369519.4	NP_001127835.2	Q5T481
RBM20	XM_017016103.3 link	c.1362+8C>T	splice_region_variant, intron_variant	Intron 5 of 13		XP_016871592.1
RBM20	XM_017016104.3 link	c.1143+8C>T	splice_region_variant, intron_variant	Intron 5 of 13		XP_016871593.1
RBM20	XM_047425116.1 link	c.1143+8C>T	splice_region_variant, intron_variant	Intron 5 of 13		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4 link	c.1527+8C>T		splice_region_variant, intron_variant	Intron 5 of 13	1	NM_001134363.3	ENSP00000358532.3		Q5T481
RBM20	ENST00000718239.1 link	c.1527+8C>T		splice_region_variant, intron_variant	Intron 5 of 13			ENSP00000520684.1

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31898

AN:

151950

Hom.:

3479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.177

Gnomad EAS

AF:

0.0870

Gnomad SAS

AF:

0.0997

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.192

GnomAD2 exomes

AF:

0.185

AC:

25732

AN:

139300

AF XY:

0.180

show subpopulations

Gnomad AFR exome

AF:

0.229

Gnomad AMR exome

AF:

0.161

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.0828

Gnomad FIN exome

AF:

0.223

Gnomad NFE exome

AF:

0.224

Gnomad OTH exome

AF:

0.188

GnomAD4 exome

AF:

0.209

AC:

270142

AN:

1292076

Hom.:

29496

Cov.:

AF XY:

0.206

AC XY:

131831

AN XY:

640486

show subpopulations

African (AFR)

AF:

0.219

AC:

6290

AN:

28778

American (AMR)

AF:

0.164

AC:

5117

AN:

31220

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

4247

AN:

23984

East Asian (EAS)

AF:

0.0695

AC:

2445

AN:

35174

South Asian (SAS)

AF:

0.103

AC:

7553

AN:

73364

European-Finnish (FIN)

AF:

0.226

AC:

11079

AN:

49092

Middle Eastern (MID)

AF:

0.112

AC:

611

AN:

5458

European-Non Finnish (NFE)

AF:

0.224

AC:

222087

AN:

990560

Other (OTH)

AF:

0.197

AC:

10713

AN:

54446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

9455

18910

28366

37821

47276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7410

14820

22230

29640

37050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.210

AC:

31939

AN:

152068

Hom.:

3489

Cov.:

AF XY:

0.207

AC XY:

15415

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.221

AC:

9157

AN:

41438

American (AMR)

AF:

0.186

AC:

2849

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

614

AN:

3466

East Asian (EAS)

AF:

0.0866

AC:

449

AN:

5182

South Asian (SAS)

AF:

0.0995

AC:

479

AN:

4812

European-Finnish (FIN)

AF:

0.221

AC:

2337

AN:

10576

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.228

AC:

15470

AN:

67976

Other (OTH)

AF:

0.194

AC:

411

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1315

2629

3944

5258

6573

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

332

664

996

1328

1660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.216

Hom.:

16182

Bravo

AF:

0.207

Asia WGS

AF:

0.119

AC:

416

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Sep 27, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 26, 2012

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dilated cardiomyopathy 1DD

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Primary dilated cardiomyopathy

Benign:1

Sep 27, 2022

Cohesion Phenomics

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.6

(source)

DANN

Benign

0.45

PhyloP100

-0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over